Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12619000208101
Ethics application status
Approved
Date submitted
27/11/2018
Date registered
13/02/2019
Date last updated
9/02/2021
Date data sharing statement initially provided
13/02/2019
Date results information initially provided
9/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Understanding the utilisation of an insulin-to-protein ratio in people with type 1 diabetes who follow a carbohydrate-restricted diet.
Scientific title
Understanding the utilisation of an insulin-to-protein ratio in people with type 1 diabetes who follow a carbohydrate-restricted diet.
Secondary ID [1] 296691 0
Nil known
Universal Trial Number (UTN)
U1111-1224-5507
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes Mellitus 310536 0
Condition category
Condition code
Metabolic and Endocrine 309246 309246 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Brief name: Mealtime insulin dosing for both carbohydrate and protein self-administered by sub-cutaneous injection.

For 3 months, participants will self-administer a mealtime protein-based insulin bolus that is calculated using the insulin-to-protein ratio of half the carbohydrate ratio. This is in addition to insulin dosing based on mealtime carbohydrate and the participant's individualised carbohydrate ratio. This will be done using their standard insulin administration method and during their normal daily routine.

Training: We are expecting that participants will already be able to carbohydrate count. We will go over the participant's understanding with them. The training will be delivered by the researcher face-to-face at the centre for diabetes & endocrine research at Wellington hospital. Patient's will be given a written hand-out at the same time. This will occur once at the beginning of the study.

Adherence will be recorded using diary recordings of diet and insulin dosing. There will also be once-weekly phone calls for the duration of the study.

The freestyle libre is a continuous glucose monitor that consists of a small glucose sensor that sits under the skin and is attached to a water resistant patch on the skin. It reads blood glucose and trend information. A touchscreen reader device, when held near the patch, will give real-time glucose value. The sensor patch stays implanted for 14 days. It is applied by pressing the sensor onto the applicator and pressing the applicator onto the upper arm. It will be applied to the participants arm at a face to face meeting. The participant will then wear it as they go about their daily business for the next 14 days. They will have another meeting at the end of this period where it will be removed. This happens twice during the study, once at the beginning and once at the end.
Intervention code [1] 313003 0
Treatment: Other
Comparator / control treatment
Brief name: Mealtime insulin dosing for carbohydrate content only

For 3 months, participants will self-administer insulin based on mealtime carbohydrate and the participant's individualised carbohydrate ratio. This will be done using their standard insulin administration method and during their normal daily routine.
Control group
Active

Outcomes
Primary outcome [1] 308221 0
HbA1c at three months adjusted for baseline, assessed by blood test at Endocrine, Diabetes & Research Centre, CCDHB
Timepoint [1] 308221 0
Three months after randomisation
Secondary outcome [1] 354268 0
Glycaemic variability, determined as the standard deviation of recorded blood glucose over 2 weeks by subcutaneous freestyle libre continuous blood glucose monitor.
Timepoint [1] 354268 0
Two weeks after insertions of subcutaneous freestyle libre continuous blood glucose monitor, which occurs at three months after randomisation.
Secondary outcome [2] 354269 0
Proportion of time the blood glucose was 4.0-8.0mmol/L, collected over 2 weeks by subcutaneous freestyle libre continuous blood glucose monitor.
Timepoint [2] 354269 0
Two weeks after insertions of subcutaneous freestyle libre continuous blood glucose monitor, which occurs at three months after randomisation.
Secondary outcome [3] 354273 0
Proportion of time the blood glucose was less than 4.0mmol/L, collected over 2 weeks by subcutaneous freestyle libre continuous blood glucose monitor.
Timepoint [3] 354273 0
Two weeks after insertions of subcutaneous freestyle libre continuous blood glucose monitor, which occurs at three months after randomisation.
Secondary outcome [4] 366379 0
Qualitative assessment of quality of life, acceptability and ease of use of insulin dosing regimen, using a study-specific questionnaire
Timepoint [4] 366379 0
Three months after randomisation.
Secondary outcome [5] 391630 0
Mean blood glucose from 2 weeks of subcutaneous freestyle libre continuous blood glucose monitor. This change was made after all participants had finished the study.
Timepoint [5] 391630 0
Two weeks after insertion of subcutaneous freestyle libre continuous blood glucose monitor, which occurs at three months after randomisation.
Secondary outcome [6] 391631 0
Proportion of time blood glucose was greater than 8.0mmol/L, collected over 2 weeks by subcutaneous freestyle libre continuous blood glucose monitor.
Timepoint [6] 391631 0
Two weeks after insertions of subcutaneous freestyle libre continuous blood glucose monitor, which occurs at three months after randomisation.
Secondary outcome [7] 391632 0
Proportion of time blood glucose was 8.0-12.0mmol/L collected over 2 weeks by subcutaneous freestyle libre continuous blood glucose monitor.
Timepoint [7] 391632 0
Two weeks after insertions of subcutaneous freestyle libre continuous blood glucose monitor, which occurs at three months after randomisation.
Secondary outcome [8] 391633 0
Proportion of time blood glucose was greater than 12.0mmol/L collected over 2 weeks by subcutaneous freestyle libre continuous blood glucose monitor.
Timepoint [8] 391633 0
Two weeks after insertions of subcutaneous freestyle libre continuous blood glucose monitor, which occurs at three months after randomisation.

Eligibility
Key inclusion criteria
People with type 1 diabetes mellitus who follow a basal-bolus insulin regimen and attend diabetes clinics at Capital and Coast Health.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pregnant or planning pregnancy
Breast-feeding
Unstable diabetes control (HbA1c>85 mmol/mol)
Kidney disease (EGFR<30 or on dialysis)
Hypoglycaemia unawareness, defined as a recurrent failure to detect a significant fall in blood glucose below normal levels
People who undertake more than 15 hours of moderate to intense exercise per week
History of gastroparesis

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The study was powered using data from an identical insulin dosing intervention in a sample of 16 participants. In this study the primary outcome was the count of blood glucose values = 8 mmol/l observed during a set of eight timed venous blood samples following a meal challenge. The meal challenge was repeated on 3 occasions for each of the protein dosing arm and conventional carbohydrate dosing arm. The generalised linear mixed model for this study incorporated individuals as random effects to account for correlation of repeated measures and the intervention arm was specified as a fixed effect, the number of repeated measures on each occasion was used as the offset variable. A simulation method for generalised linear mixed models, simr, was used to assess the expected rate ratio of 0.72 when comparing the protein dosing arm to the carbohydrate dosing arm. A sample size of 30 yielded a power of 80% with a Type I error rate of 5% to detect a rate ratio of 0.72. The simulation model is identical to the planned generalized linear model appropriate for the design of this study.

The current study will have far more frequent repeated measures, >2000 per participant, based on recordings every five minutes for seven days. A sample size of 36 was chosen to account for a 10% loss due to drop out.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
19/02/2019
Actual
29/03/2019
Date of last participant enrolment
Anticipated
1/08/2019
Actual
9/09/2019
Date of last data collection
Anticipated
31/10/2019
Actual
11/12/2019
Sample size
Target
36
Accrual to date
Final
34
Recruitment outside Australia
Country [1] 21063 0
New Zealand
State/province [1] 21063 0
Wellington

Funding & Sponsors
Funding source category [1] 301268 0
Charities/Societies/Foundations
Name [1] 301268 0
Maurice and Phyllis Paykel Trust
Country [1] 301268 0
New Zealand
Funding source category [2] 301270 0
Other
Name [2] 301270 0
Private Donor
Country [2] 301270 0
New Zealand
Primary sponsor type
Hospital
Name
Capital and Coast District Health Board
Address
Wellington Regional Hospital
Private Bag 7902
Wellington 6242
Country
New Zealand
Secondary sponsor category [1] 300950 0
None
Name [1] 300950 0
Address [1] 300950 0
Country [1] 300950 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302011 0
Northern A Health and Disability Ethics Committee
Ethics committee address [1] 302011 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 302011 0
New Zealand
Date submitted for ethics approval [1] 302011 0
Approval date [1] 302011 0
28/01/2019
Ethics approval number [1] 302011 0

Summary
Brief summary
Thirty six people with T1DM attending diabetes clinics at Capital and Coast Health will be invited to take part in a randomised controlled trial of mealtime insulin dosing for carbohydrate content only compared with dosing for both carbohydrate and protein.

Participants will follow a carbohydrate-restricted diet (= 100g of carbohydrate per day) for three months. Before randomisation, participants who are not already following this diet will receive help to transition. All participants will have a subcutaneous freestyle libre continuous glucose monitor inserted and two weeks of glucose data will be collected. After baseline measurements, including HbA1c, participants will be randomised to either group, and receive training on estimating carbohydrate and protein content in their meals. Individual carbohydrate ratios will be established and the additional protein bolus be calculated using the insulin-to-protein ratio of half the carbohydrate ratio. After three months participants will have another subcutaneous freestyle libre continuous glucose monitor inserted. Two weeks of glucose data will be collected, and participants will have a blood test for HbA1c.

The primary outcome is HbA1c at three months.

The findings of this study will identify the effect of an additional insulin bolus based on dietary protein and carbohydrate on blood glucose in people with T1DM following a carbohydrate-restricted diet in real world conditions.
Trial website
Trial related presentations / publications
Public notes
Final ethics approval was received on 20/02/2019.

Contacts
Principal investigator
Name 88846 0
Prof Jeremy Krebs
Address 88846 0
Capital & Coast District Health Board
Level 5, Grace Neill Block
Private Bag 7902
Wellington South
Wellington 6021
New Zealand
Country 88846 0
New Zealand
Phone 88846 0
+64 (04) 806 2458
Fax 88846 0
+64 (04) 3855948
Email 88846 0
[email protected]
Contact person for public queries
Name 88847 0
Prof Jeremy Krebs
Address 88847 0
Capital & Coast District Health Board
Level 5, Grace Neill Block
Private Bag 7902
Wellington South
Wellington 6021
New Zealand
Country 88847 0
New Zealand
Phone 88847 0
+64 (04) 806 2458
Fax 88847 0
+64 (04) 3855948
Email 88847 0
[email protected]
Contact person for scientific queries
Name 88848 0
Prof Jeremy Krebs
Address 88848 0
Capital & Coast District Health Board
Level 5, Grace Neill Block
Private Bag 7902
Wellington South
Wellington 6021
New Zealand
Country 88848 0
New Zealand
Phone 88848 0
+64 (04) 806 2458
Fax 88848 0
+64 (04) 3855948
Email 88848 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual requests for data sharing will be considered.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1339Study protocol    376447-(Uploaded-12-02-2019-08-18-53)-Study-related document.docx



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Basic resultsNo 376447-(Uploaded-16-06-2020-14-09-07)-Basic results summary.docx
Plain language summaryNo A total of 34 participants were recruited of which... [More Details]

Documents added automatically
No additional documents have been identified.